ASCO Roundup: Rare Melanomas and Skin Cancers

At the ASCO Annual Meeting, a variety of investigators presented results that could change practice for patients with rare types of melanoma and skin cancers. Several presenters highlighted their findings.

Orloff on the OptimUM-02 Trial in Metastatic Uveal Melanoma

In one of the most significant presentations in melanoma, Marlena Orloff, MD, of Thomas Jefferson University, discussed findings from the phase 2b portion of the OptimUM-02 trial (NCT05987332) evaluating davosertib plus crizotinib as first-line treatment for patients with metastatic uveal melanoma who are HLA-A*02:01 negative. The randomized global study met its primary end point, demonstrating a statistically significant improvement in progression-free survival (PFS) compared with investigator’s choice therapy. Median PFS was 5.9 months with davosertib/crizotinib vs 3.1 months in the control arm, which primarily consisted of combination immunotherapy. Secondary end points, including overall response rate (ORR) and disease control rate, also favored the investigational regimen, supporting its potential as a practice-changing targeted therapy in a space with no approved treatments.

Cadonilimab, Ivonescimab, and Axitinib in Mucosal Melanoma

Lili Mao, MD, of Peking University Cancer Hospital, reviewed results from a phase 1b study (NCT06424626) evaluating the combination of axitinib (Inlyta) with investigational bispecific antibodies, cadonilimab, and ivonescimab, in patients with mucosal melanoma. Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, while ivonescimab targets PD-1 and VEGF. The trial’s primary objective was safety, and the regimen demonstrated a manageable toxicity profile, with treatment-related adverse events occurring in 71% of patients and grade 3 events in 18%. Efficacy outcomes were more modest than anticipated when compared with historical controls using PD-1/PD-L1 inhibitors, with an ORR of 35.7% in both cohorts. Median PFS was 5.8 months in the cadonilimab cohort and 8.3 months in the ivonescimab cohort.

The ADAM Trial in Merkel Cell Carcinoma

Shailender Bhatia, MD, of Fred Hutch Cancer Center, highlighted results from the phase 3 ADAM trial (NCT03271372), an investigator-initiated study evaluating adjuvant avelumab (Bavencio) in Merkel cell carcinoma conducted across multiple academic centers. The safety profile was consistent with prior experience using immune checkpoint inhibitors, with approximately 15% of patients experiencing grade 3 or higher treatment-related adverse events and 7% to 8% discontinuing therapy because of toxicity. The primary end point was relapse-free survival. In the placebo arm, roughly 40% of patients experienced recurrence, mostly within the first year. Avelumab reduced the relapse rate to 12%, corresponding to an absolute risk reduction of 28%.